dc.contributor.advisor | Romo, Daniel | |
dc.creator | Mitchell, Timothy Andrew 1979- | |
dc.date.accessioned | 2019-01-25T21:46:43Z | |
dc.date.available | 2019-01-25T21:46:43Z | |
dc.date.created | 2008-05 | |
dc.date.issued | 2009-05-15 | |
dc.date.submitted | May 2008 | |
dc.identifier.uri | https://hdl.handle.net/1969.1/174656 | |
dc.description.abstract | Although initial attempts to convert (R)-4-trichloromethyl-β-lactone to
ketoaldehydes or keto-β-lactones for stereoselective tetrahydrofuran (THF) synthesis
were unsuccessful, several novel transformations of this malic acid surrogate were
discovered. Radical alkylations and α-silylations of optically active (R)-trichloromethyl-
2-oxetanone are described that maintain the integrity of the β-lactone. Alternate
methods for selective dechlorinations of both the β-lactone and the derived Weinreb
amide are presented.
The development of a diastereoselective, three-step strategy for the construction
of substituted tetrahydrofurans from alkenyl-aldehydes based on the tandem Mukaiyama
aldol-lactonization (TMAL) process and Mead reductive cyclization of keto-β-lactones
is reported. Stereochemical outcomes of the TMAL process are consistent with models
established for Lewis acid-mediated additions to α-benzyloxy and β-silyloxy aldehydes
while reductions of the five-membered oxocarbenium ions are consistent with Woerpel’s models. Further rationalization for observed high diastereoselectivity in reductions of α-
silyloxy five-membered oxocarbenium ions based on stereoelectronic effects is posited.
A diagnostic trend for coupling constants of γ-benzyloxy-β-lactones was observed that
should enable assignment of the relative configuration of these systems.
A single stereocenter generates as many as two C-C bonds, one C-O bond, and
three stereocenters in a single reaction leading to substituted tetrahydrofurans (THFs) in
a three-component process. This process utilizes the tandem Mukaiyama aldollactonization
(TMAL) and proceeds through a silylated β-lactone intermediate. The
results build on Mead’s reductive cyclization (MRC) of keto-β-lactones and are in
accordance with Woerpel’s model for “inside attack” of oxocarbenium ions.
Application to a THF fragment of colopsinol B is described.
A universal model was set forth that rationalizes the stereochemical outcome of
the reaction between α- and β-substituted aldehydes and (E)- and (Z)-substituted ketene
acetals in the ZnCl2-mediated tandem Mukaiyama aldol-lactonization (TMAL). | en |
dc.format.mimetype | application/pdf | |
dc.subject | beta-lactone | en |
dc.subject | tetrahydrofuran | en |
dc.subject | oxocarbenium | en |
dc.subject | reductive cyclization | en |
dc.subject | tandem | en |
dc.subject | Mukaiyama aldol | en |
dc.subject | radical | en |
dc.title | Development of a tandem, three-component synthesis of tetrahydrofurans via silylated beta-lactone intermediates in the tandem Mukaiyama aldol-lactonization | en |
dc.type | Thesis | en |
thesis.degree.department | Chemistry | en |
thesis.degree.discipline | Chemistry | en |
thesis.degree.grantor | Texas A & M University | en |
thesis.degree.name | Doctor of Philosophy | en |
thesis.degree.level | Doctoral | en |
dc.contributor.committeeMember | Bergbreiter, David | |
dc.contributor.committeeMember | Kenerley, Charles | |
dc.contributor.committeeMember | Singleton, Daniel | |
dc.type.material | text | en |
dc.date.updated | 2019-01-25T21:46:44Z | |